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OBJECTIVES: We aimed to raise awareness among paediatricians and physicians about this often misunderstood condition. METHODS: We discussed the clinical profiles associated with late or wrong diagnosis of mevalonate kinase deficency (MKD) in a single centre case series. RESULTS: We analysed the most common challenges and pitfalls that a clinician might face during the diagnostic process. Five main clinical profiles were characterised. CONCLUSIONS: We propose a new perspective on MKD, suggesting that the presentation of this disease can vary from patient to patient.

In response to the binding of extracellular ligands to cell surface receptors, multiple transcription factors are activated in the cytoplasm and translocated into the nucleus where they exert positive or negative control over cellular genes. The human transcription factor NF-kappa B family regulates the expression of a large number of genes involved in the host defence mechanism. They are typically present in the cytoplasm bound to the inhibitory I kappa B proteins. The activation of NF-kappa B involves the signal-induced degradation of these proteins, allowing NF-kappa B to translocate to the nucleus. In this study, by multiparametric analysis, we recognise in RPMI-8402 DMSO-activated cells the intracellular movement of transcription factor NF-kappa B providing its definite intranuclear collocation. Intact cells, purified nuclei and nuclear matrix preparations after 4 h of treatment were processed for morphological and biochemical analyses. Light and electron microscope observations show, in untreated cells, the presence of NF-kappa B protein homogeneously retained in the cytoplasm. Treated cells display a massive presence of NF-kappa B at the nuclear level bound to the interchromatin region. Immunoblotting of the same specimens confirms the strong association of NF-kappa B with the nuclear scaffold. Taken together, the data presented in this manuscript support a model where DMSO treatment provokes the cleavage and translocation of NF-kappa B from the cytoplasm to the nucleus and, in particular, in the proteinaceous network of the nuclear matrix sustaining the active role of this subcellular structure on regulation of eukaryotic gene expression.

The regulation of cell proliferation or cell death by extracellular factors are the most intensely studied subjects in cell biology. Many conceptual problems remain to be clarified concerning the mechanisms that regulate the programmed cell death. In this work, we focus our attention on the possible role of protein kinase C activation during dimethyl sulfoxide (DMSO)-induced cell death. The present results suggest that the frequency of DMSO-dependent apoptosis of RPMI 8402 thymic lymphoma cells is increased by phorbol ester acetate supplementation. Enhancement of apoptosis can be abolished by cotreatment with the bisindolylmaleimide, a specific PKC inhibitor. The association between PMA and DMSO treatment provokes an early activation of an intracellular signaling mechanism that results, via sustained diacylglycerol elevation, in a possible long-term PKC activation.

Molecular interaction and transmembrane signal transducing events generate a very dynamic and ever changing «pattern» in the plasma membranes. Lymphocytes, the key functional elements of the immune system, are eminently suited to be the primary targets to investigate these proximity, mobility, or other physical-chemical changes in their plasma membranes. Recently, a number of experiments suggested that processed peptides from antigens can bind specific components of MHC molecules ( Elliott et al., 1991 ). This is certainly a way to alter their structure. Cell surface patterns of topological nature, assembly and disassembly of oligomeric receptor structure like the IL-2 receptor have been investigated by sophisticated biophysical techniques. The dynamic changes in the two-dimensional cell surface pattern and intramolecular conformational changes within this «larger» macro-pattern may have a strong regulatory role in signal transducing and intercellular recognition processes. Recent data on these problems are presented together with brief and critical discussions.

Part One of this book introduces the challenges of monitoring and evaluating interventions designed by technical experts meeting the needs of people who actually use the environment which the interventions are seeking to modify. The chapters in this section seek reconciliation of these tensions through a variety of techniques that seek to engage non-expert voices in providing information and in return offer various degrees of ownership of the interventions. Part Two offers a range of case studies that show monitoring and evaluation in practice in a range of contexts in Africa, Asia and Latin America. Rich, thick descriptions bring out the challenges faced in practice in the field. Various ways forward are offered including greater institutionalisation of monitoring and evaluation in the State, but most point to greater inclusion of people affected by the interventions in the information system – looking to greater influence on decision-making. Part Three explores the frontiers of the contributions of physical science to monitoring and evaluating soil conservation and watershed management. The chapters demonstrate the increasing capacities of physical science to measure changes in the physical environment. The technical sophistication and ingenuity of the techniques is striking for a social scientist. Even the residues of nuclear tests and the Chernobyl disaster can be used to show how soils have moved over the past fifty years. Part Four engages more directly with the inevitable complications when monitoring and evaluation meets the socio-economic organisation of knowledge. The chapters bring out the resource implications of engaging with complex civil societies in a range of contexts from the highly individualistic in the USA to techno-bureaucratically dominated in Pakistan. The book offers accounts of socio-environmental processes in a wide range of contexts. It also has some of the qualities of a manual in offering numerous Tables with checklists of key variables plus a general concern with forefronting observability of performance and developmental impact.

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